At the time this renewal proposal was funded we had successfully addressed three initial specific aims which represented the groundwork of our synthetic strategy. Since then we have focused our efforts on the following specific aims: (1) Stereospecific elaboration of appropriate C10-C21 precursors having C15 at various oxidation states for the maytansinoids. (2) Stereocontrolled synthesis of C1-C8 "northern zone" fragments. (3) Coupling of appropriate C1-C8 and C10-C21 units at the C9 linchpin.